Upstream reactive oxidative species (ROS) signals in exogenous oxidative stress‐induced mitochondrial dysfunction

Abstract

Exogenous oxidative stress induces cell death, but the upstream molecular mechanisms involved of the process remain relatively unknown. We determined the instant dynamic reactions of intracellular reactive oxygen species (ROS, including hydrogen peroxide (H(2)O(2)), superoxide radical (O(2)(*)(-)), and nitric oxide (NO)) in cells exposed to exogenous oxidative stress by using a confocal laser scanning microscope. Stimulation with extracellular H(2)O(2) significantly increased the production of intracellular H(2)O(2), O(2)(*)(-), and NO (P<0.01) through certain mechanisms. Increased levels of intracellular ROS resulted in mitochondrial dysfunction, involving the impairment of mitochondrial activity and the depolarization of mitochondrial membrane potential. Mitochondrial dysfunction significantly inhibited the proliferation of human hepatoblastoma G2 (HepG2) cells and resulted in mitochondrial cytochrome c (cyt c) release. The results indicate that upstream ROS signals play a potential role in exogenous oxidative stress-induced cell death through mitochondrial dysfunction and cyt c release.

Oxidative DNA damage induced by di-(2-ethylhexyl) phthalate in HEK-293 cell line

“…It has been recognized that mitochondrial dysfunction appears to promote ROS production (Lu and Gong, 2009). …”

Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction

“…One commonly used oxidant, hydrogen peroxide (H 2 O 2 ) is freely diffusible within the cell and causes a wide range of effects based on concentration and cell type, including an increase in mtDNA damage compared to nDNA damage (nuclear DNA) [3,4,6,22,23], mtDNA degradation [10], increased mitochondrial mass [24], cell growth arrest [3,25-29], apoptosis [6,29-31], autophagy [31], increased secondary ROS such as H 2 O 2 and superoxide [32], and decreased antioxidant activity [33,34]. However, the only study linking oxidative stress to a decrease in mitochondrial function is a 2001 study by Szweda and Nulton-Persson, which suggested that H 2 O 2 treatment of isolated rat heart mitochondria caused a reversible decline in oxidative phosphorylation [34].…”

Lycium barbarum Polysaccharides Attenuate Cisplatin-Induced Hair Cell Loss in Rat Cochlear Organotypic Cultures

“…ROS generation in cisplatin-treated hair cells was closely correlated with its ototoxicity. An increased ROS will cause a decrease of mitochondrial membrane potential, which alters cellular energy production and starts mechanisms for the execution of apoptosis [20,23]. Our results showed that exposure to cisplatin (20 μM) for 6 h increased the generation of ROS in hair cells and about a two-fold increase in ROS production 48 h after cisplatin exposure.…”

“…Mitochondrial ROS burst is an early upstream apoptotic signal. Oxidative damage to mitochondria causes the impairment of mitochondrial function and subsequently leads to cell death via apoptosis and necrosis [20–22]. Therefore, we investigated the level of ROS in organ of Corti explant using DCFH-DA.…”